Oral Chinese herbal medicine for psoriasis vulgaris: protocol for a randomised, double-blind, double-dummy, multicentre clinical trial.
Psoriasis vulgaris is a common skin disease that is characterised by persistent localised erythematous scaly plaques. Yinxieling is a Chinese herbal formula for psoriasis that has been used for more than 20 years in China. To facilitate application, PSORI-CM01 was developed based on the optimisation and simplification of Yinxieling tablets performed in a previous study and in clinical practice. However, the scientific evidence regarding whether PSORI-CM01 is more effective for psoriasis than the original Yinxieling remains insufficient. Therefore, we designed a randomised clinical trial to investigate the effect, safety and cost-effectiveness of PSORI-CM01 granules compared with those of Yinxieling tablets for the treatment of patients with psoriasis. This ongoing study is a two-arm parallel, randomised, double-blind, double-dummy clinical trial. Five hundred and fifty-six participants with psoriasis will be recruited and then randomly allocated into two groups in a 1:1 ratio. Participants in PSORI-CM01 group will receive a 5.5 g granule of PSORI-CM01 two times daily and five placebo tablets three times daily for 12 weeks. The participants in the Yinxieling group will receive five Yinxieling tablets three times daily and a placebo granule two times daily for 12 weeks. The primary outcome is the reduction of the Psoriasis Area and Severity Index. The secondary outcomes include relapse rate, Visual Analogue Scale scores, body surface area and the Dermatology Life Quality Index. Cost-effectiveness analysis will be performed from a health and community care provider perspective. This research protocol had been reviewed and approved by the institutional review boards of three trial centres (Guangdong Provincial Hospital of Chinese Medicine (B2014-026-01), Affiliated Hospital of Tianjin Chinese Medicine Academy (2014-KY-001) and Third Hospital of Hangzhou (B2014-026-01)). The findings will be disseminated to the public through conference presentations and open-access journals. Chinese Clinical Trial Registry (ChiCTR-TRC-14005185); Pre-results.


Verapamil abolishes the preglomerular response to ANG II during intrarenal nitric oxide synthesis inhibition.
We have recently reported that intrarenal nitric oxide (NO) synthesis inhibition exaggerates the preglomerular vasoconstrictor response more than the postglomerular response to angiotensin II (ANG II) in dogs. Previous studies have suggested that preglomerular vasoconstriction may be more dependent on extracellular calcium than postglomerular vasoconstriction. The purpose of this study is to determine whether the enhanced preglomerular response to ANG II during intrarenal NO synthesis inhibition occurs through voltage-gated calcium channels. In three groups of anesthetized dogs with stop-flow kidneys, the renal hemodynamic response to intrarenal ANG II infusion (2.0 ng.kg-1.min-1) was determined. Renal artery pressure was servo-controlled at 80 +/- 1 mmHg, and glomerular filtration rate was zero. In vehicle-treated dogs, ANG II decreased renal blood flow (RBF) by 29% and increased glomerular hydrostatic pressure (Pg) by 2.7 +/- 1.9 mmHg. Postglomerular vascular resistance increased by 51%, whereas preglomerular resistance was unchanged in response to ANG II. In dogs pretreated with an intrarenal infusion of NG-nitro-L-arginine methyl ester (L-NAME; 5 micrograms.kg-1.min-1) for 60 min, ANG II decreased RBF by 36% and decreased Pg 4.4 +/- 2.9 mmHg. In contrast to the vehicle-treated group, preglomerular resistance increased by 261% and postglomerular resistance increased by 48% after ANG II infusion in the L-NAME-treated group. In dogs pretreated with an intrarenal infusion of L-NAME and verapamil (50 micrograms/min) for 60 min, the renal hemodynamic response to ANG II was similar to the response in the vehicle-treated dogs. ANG II decreased RBF by 25% and decreased Pg by 5.3 +/- 1.2 mmHg. Postglomerular resistance increased by 51%, whereas preglomerular resistance was unchanged in response to ANG II infusion in dogs with intrarenal NO synthesis and voltage-gated calcium channel blockade. These data indicate that the preglomerular response to ANG II under conditions of reduced NO synthesis within the kidney is dependent on voltage-gated calcium channels.


Hepatitis B virus surface antigen seroconversion in HIV-infected individual after pegylated interferon-alpha treatment: a case report.
Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm3), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.


A challenging hernia: primary venous aneurysm of the proximal saphenous vein.
Primary venous aneurysm is a rare, but essential consideration in the differential diagnosis of an inguinal and femoral hernia. We report a case of a 43-year-old man who was referred for evaluation and treatment of a femoral hernia. The patient presented with a 3-month history of an asymptomatic tumor on his right upper inner thigh. Physical examination noted a non-tender, non-indurated tumor. Surgical exploration demonstrated a primary venous aneurysm of the proximal saphenous vein.


Association of nonalcoholic fatty liver disease with colorectal adenomatous polyps and non-adenomatous polyps: a cross-sectional study.
This study aimed to investigate the association between non-alcoholic fatty liver disease (NAFLD) and both colorectal adenomatous polyps and non-adenomatous polyps, in order to provide evidence for the prevention of colorectal cancer (CRC) in patients with NAFLD. A retrospective, cross-sectional study was conducted at the First People's Hospital of Kunshan, Jiangsu, China. The study included 3028 adults who underwent abdominal ultrasonography and colonoscopy over a 5 year period. We compared characteristics among patients with adenomatous polyps, non-adenomatous polyps, and without colorectal polyps using descriptive statistics. Logistic regression analyses were used to detect associations between NAFLD with the prevalence of adenomatous polyps and non-adenomatous polyps. NAFLD was determined by abdominal ultrasound. Colorectal polyps were assessed by data in the colonoscopy report and pathology report. A total of 65% of patients with NAFLD had colorectal polys (52% adenomatous polyps and 13% non-adenomatous polyps), and 40% of patients without NAFLD had polyps (29% adenomatous polyps and 11% non-adenomatous polyps). After adjusting for confounding variables, NAFLD was significantly associated with the prevalence of adenomatous in males and females [odds ratio (OR) = 1.8, 95% confidence interval (CI): 1.6-2.2, P < 0.01], but was not associated with non-adenomatous polyps (OR = 1.2, 95% CI:0.9-1.5, P > 0.05). NAFLD is associated with an increased risk of colorectal adenomatous polyps compared to the absence of polyps, but not associated with an increased risk of non-adenomatous polyps. These results provide important evidence for the prevention of CRC in patients with NAFLD.


Primary Rosai-Dorfman disease of the bone in a patient with history of breast cancer: appearance on 99mTc-MDP scintigraphy, CT, and X-ray.
A 49-year-old woman with history of breast cancer presented with pain at the level of the left anterior proximal tibia. An x-ray of the tibia demonstrated a lytic cortical lesion that prompted a whole-body 99mTc-MDP bone scan. The bone scan revealed intense bone remodeling at the level of the tibial lytic lesion and in the cervical spine. CT demonstrated an expansile lesion eroding the vertebral bodies of C6 and C7 with a large soft tissue component. A biopsy of the cervical spine mass demonstrated features diagnostic of Rosai-Dorfman disease without evidence of neoplastic cells.


Meeting the need for childhood cataract surgical services in Madagascar.
Cataract has emerged as the most important cause of blindness in children worldwide, and has been one of the priorities of VISION 2020, the global initiative to eliminate avoidable blindness by 2020. More than 2500 children are estimated to be blind from cataract in Madagascar. The aim of this study was to investigate the burden and causes of pediatric cataract in a busy eye clinic in Madagascar and measure service delivery. This was a retrospective case series of all children aged 15 and below, receiving cataract surgery at the busiest eye clinic in Southern Madagascar. Data on all children operated on at the eye clinic between September 1999 and July 2009 were retrieved from theatre logs and patient charts. One hundred and fourteen eyes of 86 children were operated on during the study period, with congenital cataract being the diagnosis in 53.5% of the children. For the catchment area of 5.8 million inhabitants 2.7% of incident cases of non-traumatic pediatric cataracts had surgery, with a mean CCSR per year for the entire catchment area of 1.1/million population. The Southern part of Madagascar is underserved for pediatric cataract surgical services, hence the need for a childhood blindness program.


Acute gastric volvulus due to congenital bands in a newborn case.
Acute gastric volvulus in the newborn period is a rare condition requiring surgery. The association of gastric volvulus with congenital bands is extremely rare and unreported previously. A one-day-old male neonate was diagnosed to have acute gastric obstruction in the neonatal intensive care unit. Mesenteroaxial gastric volvulus due to dense gastrocolic bands was detected during laparotomy. Band excision and anterior gastropexy were performed. The clinical features, radiologic findings, treatment modes and possible mechanisms of gastric volvulus due to congenital bands are discussed.


Assessing Facilitator Fidelity to Principles of Public Deliberation: Tutorial.
Public deliberation, or deliberative democracy, is a method used to elicit informed perspectives and justifiable solutions to ethically fraught or contentious issues that affect multiple stakeholder groups with conflicting interests. Deliberative events bring together stakeholders (deliberants) who are provided with empirical evidence on the central issue or concern and then asked to discuss the evidence, consider the issue from a societal perspective, and collectively work toward a justifiable resolution. There is increasing interest in this method, which warrants clear guidance for evaluating the quality of its use in research. Most of the existing literature on measuring deliberation quality emphasizes the quality of deliberants' inputs (eg, engagement and evidence of compromise) during deliberative sessions. Fewer researchers have framed quality in terms of facilitator inputs, and these researchers tend to examine inputs that are consistent with generic group processes. The theory, process, and purpose of public deliberation, however, are distinct from those of focus groups or other group-based discussions and warrant a mechanism for measuring quality in terms of facilitator fidelity to the principles and processes of deliberative democracy. In our public deliberation on ethical conflicts in minor consent for biomedical HIV prevention research, we assessed facilitator fidelity to these principles and processes because we believe that such assessments serve as a component of a comprehensive evaluation of overall deliberation quality. We examined verbatim facilitator remarks in the deliberation transcripts and determined whether they aligned with the 6 principles of public deliberation: equal participation, respect for the opinions of others, adoption of a societal perspective, reasoned justification of ideas, expression of diverse opinions, and compromise or movement toward consensus. In this tutorial, we describe the development of a blueprint to guide researchers in assessing facilitator fidelity, share 3 templates that will assist them in the task, and describe the results of our assessment of facilitator fidelity in 1 of the 4 sites in which we conducted deliberations.


Hydrogen evolution from a copper(I) oxide photocathode coated with an amorphous molybdenum sulphide catalyst.
Concerns over climate change resulting from accumulation of anthropogenic carbon dioxide in the atmosphere and the uncertainty in the amount of recoverable fossil fuel reserves are driving forces for the development of renewable, carbon-neutral energy technologies. A promising clean solution is photoelectrochemical water splitting to produce hydrogen using abundant solar energy. Here we present a simple and scalable technique for the deposition of amorphous molybdenum sulphide films as hydrogen evolution catalyst onto protected copper(I) oxide films. The efficient extraction of excited electrons by the conformal catalyst film leads to photocurrents of up to -5.7 mA cm(-2) at 0 V versus the reversible hydrogen electrode (pH 1.0) under simulated AM 1.5 solar illumination. Furthermore, the photocathode exhibits enhanced stability under acidic environments, whereas photocathodes with platinum nanoparticles as catalyst deactivate more rapidly under identical conditions. The work demonstrates the potential of earth-abundant light-harvesting material and catalysts for solar hydrogen production.


Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial.
Intravitreous injections of antivascular endothelial growth factor agents are effective for treating diabetic macular edema (DME) involving the center of the macula (center-involved DME [CI-DME]) with visual acuity impairment (20/32 or worse). The best approach to treating patients with CI-DME and good visual acuity (20/25 or better) is unknown. To compare vision loss at 2 years among eyes initially managed with aflibercept, laser photocoagulation, or observation. Randomized clinical trial conducted at 91 US and Canadian sites among 702 adults with type 1 or type 2 diabetes. Participants had 1 study eye with CI-DME and visual acuity of 20/25 or better. The first participant was randomized on November 8, 2013, and the final date of follow-up was September 11, 2018. Eyes were randomly assigned to 2.0 mg of intravitreous aflibercept (n = 226) as frequently as every 4 weeks, focal/grid laser photocoagulation (n = 240), or observation (n = 236). Aflibercept was required for eyes in the laser photocoagulation or observation groups that had decreased visual acuity from baseline by at least 10 letters (≥ 2 lines on an eye chart) at any visit or by 5 to 9 letters (1-2 lines) at 2 consecutive visits. The primary outcome was at least a 5-letter visual acuity decrease from baseline at 2 years. Antiplatelet Trialists' Collaboration adverse events (defined as myocardial infarction, stroke, or vascular or unknown death) were reported. Among 702 randomized participants (mean age, 59 years; 38% female [n=264]), 625 of 681 (92% excluding deaths) completed the 2-year visit. For eyes with visual acuity that decreased from baseline, aflibercept was initiated in 25% (60/240) and 34% (80/236) in the laser photocoagulation and observation groups, respectively. At 2 years, the percentage of eyes with at least a 5-letter visual acuity decrease was 16% (33/205), 17% (36/212), and 19% (39/208) in the aflibercept, laser photocoagulation, and observation groups, respectively (aflibercept vs laser photocoagulation risk difference, -2% [95% CI, -9% to 5%]; relative risk, 0.88 [95% CI, 0.57-1.35; P = .79]; aflibercept vs observation risk difference, -3% [95% CI, -11% to 4%]; relative risk, 0.83 [95% CI, 0.55-1.27; P = .79]; laser photocoagulation vs observation risk difference, -1% [95% CI, -9% to 6%]; relative risk, 0.95 [95% CI, 0.64-1.41; P = .79]). Antiplatelet Trialists' Collaboration vascular events occurred in 15 (7%), 13 (5%), and 8 (3%) participants in the aflibercept, laser photocoagulation, and observation groups. Among eyes with CI-DME and good visual acuity, there was no significant difference in vision loss at 2 years whether eyes were initially managed with aflibercept or with laser photocoagulation or observation and given aflibercept only if visual acuity worsened. Observation without treatment unless visual acuity worsens may be a reasonable strategy for CI-DME. ClinicalTrials.gov Identifier: NCT01909791.


Legal and ethical issues in the regulation and development of engineering achievements in medical technology. II.
For pt.I see ibid., vol.9, no.2, p.79-81 (1990). The ethical issues raised by the fact that patients/subjects are less protected in non-investigational-device-exemption (non-IDE) use of unapproved medical devices than in IDE use are examined. Practice, research, and nonvalidated practice, an intervention that falls into the region between pure practice and pure research, are defined and examined with respect to non-IDE use of unapproved medical devices. Two types of non-IDE use are considered: that which would be permitted under the feasibility studies mechanism, and emergency use. Ethical issues in both cases are discussed. It is concluded that the Food and Drug Administration (FDA) must not only expand the freedom of scientific investigators to develop new medical devices, allowing flexibility in defined non-IDE contexts that will not jeopardize the safety or welfare of patients, but also clearly and concisely define the procedures which outline this expanded freedom.


[Diagnosis and treatment of overweight in children and adolescents].
With regard to obesity in children and adolescents in Germany, representative data are scarce, and there are no catamnestic data on the outcome of various therapeutic interventions. The study group "Obesity in Children and Adolescents" developed evidence-based guidelines for diagnosis, treatment and prevention, which are available for diagnostic and management strategies. The implementation of the standards for day-to-day care laid down there places the family doctor at the center of things, with the task of coordinating the diagnostic and therapeutic processes. The interdisciplinary specialized doctor's office could markedly improve the care afforded to obese children and adolescents, and their families, and serve as a contact point for regional preventive activities.


Priapism induced by use of tamsulosin: A case report and review of the literature.
Numerous medications have been associated to the development of priapism as an adverse reaction, the most common are intracavernosal vasoactive agents, antipsychotics and antidepressants. Alpha blockers, in particular tamsulosin which is widely used in different urological conditions, has been associated to priapism in only few case reports. We present the case of a healthy 45-year-old man who medicated himself with two doses of 0.4 mg of tamsulosin due to a renal colic with spontaneous passage of a 3 mm stone. Eight hours after the second tamsulosin dose the patient developed a persistent painful erection not associated to sexual stimulation that lasted for 6 hours. He was admitted to the emergency room, and after history taking and physical evaluation the diagnosis of ischemic priapism was made. The patient denied consumption of any other medication or drug during the last month, blood tests in particular hemogram were normal and no recent history of pelvic trauma was reported. To achieve detumescence, five boluses of 200 mcg of phenylephrine were injected directly in the corpora cavernosa, no further procedures were needed. In the follow-up the patient had no new priapism episodes and he reported no problems with erections in sexual intercourse. Tamsulosin is one of most indicated medications in urological general practice; though priapism has been rarely associated to its consumption the risk of this side effect exists, suggesting that patients should be counselled about it.


In vitro suppression of growth of murine WEHI-3 leukemia cells and in vivo promotion of phagocytosis in a leukemia mice model by indole-3-carbinol.
Indole-3-carbinol (I3C), a potential anticancer substance, can be found in cruciferous (cabbage family) vegetables, mainly cauliflower and Chinese cabbage. However, the bioactivity of I3C on the apoptotic effects of murine leukemia WEHI-3 cells and promotion of immune responses in leukemia mice model are unclear. In this study, we investigated the effect of I3C on cell-cycle arrest and apoptosis in vitro and immunomodulation in vivo. I3C decreased the viable WEHI-3 cells and caused morphological changes in a concentration- and time-dependent manner. I3C also led to G0/G1 phase arrest, decreased the levels of cyclin A, cyclin D, and CDK2, and increased the level of p21(WAF1/CIP1). Flow cytometric analyses further proved that I3C promoted ROS and intracellular Ca(2+) production and decreased the levels of ΔΨ(m) in WEHI-3 cells. Cells after exposure to I3C for 24 h showed DNA fragmentation and chromatin condensation. Comet assay also indicated that I3C induced DNA damage in examined cells. I3C increased the levels of cytochrome c, FADD, GADD153, GRP78, and caspase-12 as well as induced activities of caspase-3, -8, and -9. Moreover, I3C attenuated NF-κB DNA binding activity in I3C-treated WEHI-3 cells as shown by EMSA and Western blotting analyses. In the in vivo study, we examined the effects of I3C on WEHI-3 leukemia mice. Results showed that I3C increased the level of T cells and decreased the level of macrophages. I3C also reduced the weights of liver and spleen, and it promoted phagocytosis by macrophages as compared to the nontreated leukemia mice group. On the basis of our results, I3C affects murine leukemia WEHI-3 cells both in vitro and in vivo.


[Calcification distributional density of the aortic-valvular complex is an independent risk factor for conduction block following self-expanding transcatheter aortic valve replacement].
To evaluate the effect of calcification distributional density in different regions of aortic-valvular complex (AVC) on postoperative new-onset conduction block (CB) following transcatheter aortic valve replacement (TAVR) using self-expandable valves (SEV) made in China. From January, 2016 to December, 2022, 73 patients with severe aortic valve stenosis received Venus-A prosthetic valve replacement using SEV made in China, and postoperative new-onset CB occurred in 18 (24.7%) of the patients. The baseline data, imaging and intervention- related data were compared were between the patients with CB and those without CB. Univariate and multivariate logistic regression analysis was used for investigating the independent risk factors for new- onset CB after TAVR, and the predictive performance of these risk factors was evaluated using receiver operating characteristic (ROC) curve and DeLong test. Compared with those with CB, the patients experiencing postoperative new-onset CB had a greater implantation depth (6.77±2.45 mm vs 5.11±3.28 mm, P=0.027), a smaller difference between the membranous septum length and the implantation depth (MSID) (0.68±3.49 mm vs 2.82±3.88 mm, P= 0.036), and a higher calcification distributional density of the left coronary sinus (LCS) in the device landing zone (DLZ) (P= 0.026). Multivariate logistic analysis revealed that DLZ-LCS calcification distributional density and MSID were independent risk (protective) factors for new-onset CB following TAVR. ROC curve analysis showed that the AUC of MSID and DLZ-LCS calcification distributional density was 0.775 and 0.716, respectively, and their combination had had a significantly higher AUC of 0.890 (P=0.041 and 0.027, respectively). The DLZ-LCS calcification distributional density is an independent risk factor for new-onset CB following TAVR using SEV. The conduction complications following TAVR can be effectively predicted using this calcification indicator combined with MSID.


A silica-based mitochondrial DNA extraction method applied to forensic hair shafts and teeth.
The purpose of this study is to evaluate the applicability of a nonorganic DNA extraction method for use in the analysis of environmentally compromised forensic hair shaft and tooth samples. The condition of the samples included cases of water decomposition, severe incineration, and varying stages of putrefaction. Enzymatic amplification and manual sequencing of the first segment of the mitochondrial hypervariable region were performed successfully on each of the 20 autopsied individuals. The results indicate that the silica-based extraction method produces mtDNA suitable for genetic identification from forensic samples including hair shafts and teeth.


Gastrointestinal stromal tumor arising in the rectovaginal septum.
We report herein a rare case of malignant gastrointestinal stromal tumor (GIST) originated from the rectal wall, which presented as a tumor on the rectovaginal septum. A 54-year-old Japanese woman, gravida 4, para 3, was admitted complaining of anuresis and severe constipation. She had a history of hysterectomy and right salpingo-oophorectomy for uterine leiomyoma 11 years previously. Pelvic examination revealed an 8.5 x 7.5 x 7.5 cm hard mass in the rectovaginal space. The inferior border of the tumor was 2 cm from the vaginal introitus and 2 cm from the anus. Computed tomography and magnetic resonance imaging showed a well-circumscribed soft-tissue mass filling the rectovaginal space. Urinary bladder and rectum were markedly compressed and displaced. Colon fiberscopy revealed invasion of the tumor into the rectal mucosa. An abdominoperineal resection of the rectum with posterior vaginal wall resection and pelvic lymphadenectomy was performed. The resected specimen showed a rectal submucosal tumor that was 8 x 8 x 7 cm in size. The tumor was diagnosed as a malignant GIST. Immunohistochemical analysis confirmed this diagnosis. The patient is now healthy without evidence of recurrence at 13 months after surgery. Gynecologists should be aware of rectal GIST arising in the rectovaginal space as a differential diagnosis of vaginal submucosal tumor.


[Effect of vulcanizing accelerants on embryolethality in rats].
Embryonal lethality (EL) in rats was examined after administration of the rubber accelerators (RA), captax, altax, santocure, santocure-mor and thiurams D and E. Administration of RA to non-pregnant females caused the increase in the estrous cycle and diminished the rate of conception. The total EL increased after administering all the RA, while the postimplantation one only after altax administration. The index of altax mutagenicity is comparable with those of cancerogens or alkylating agents. Administration of RA to pregnant females leads to the increase in the total EL, with altax being the single agent that produces the rise in all the types of lethality. Inhibition of reproduction function of white rats is a consequence of mutagenic, embryotic and gonadotropic actions of RA, with altax being found the most active agent.


[100 years of drinking water regulation. Retrospective review, current situation and prospects].
There is considered the history of the development of legislative requirements to the regulation of the quality of drinking water in different countries and international organizations during the period from 1912 to the present time. In terms of comparative analysis there is analyzed the current state of regulatory frameworks of the Russian Federation, WHO, EU, Finland, the UK, Singapore, Australia, Japan, China, Nigeria, the United States and Canada in the field of providing favorable conditions of population drinking water use. There has been noted the significant progress in standardization of the content of the biogenic elements and chemical pollution of drinking water in the absence of uniform requirements to the composition and properties of drinking water globally, that is bound to the need to take into account the national peculiarities of drinking water supply within the separate countries. As promising directions for improving regulation of drinking water quality there are noted: the development of new standards for prioritized water pollution, periodic review ofstandards after appearance of the new scientific data on the biological action of substances, the use of the concept of risk, the harmonization of the normative values and the assessment of the possibility of introduction into the practice the one more criterion of profitableness of population water use--the bioenergetic state of the water.


Ecto-ADP-ribosyltransferases (ARTs): emerging actors in cell communication and signaling.
Mammalian ecto ADP-ribosyltransferases (ARTs) constitute a family of structurally related proteins expressed on the cell surface or secreted in the extracellular compartment. Using NAD+ as substrate, they transfer ADP-ribose groups onto target proteins. In contrast to intracellular poly(ADP-ribosyl)transferases (PARPs), these enzymes transfer a single ADPR and are thus mono-ARTs. Five paralogs (ART1-5) have been cloned but only four of them are expressed in human due to a defective ART2 gene, and six in the mouse as the result of ART2 gene duplication. The recent determination of the crystal structure of rat ART2 reveals homologies with bacterial ART toxins and provides a molecular basis for understanding the specificity of ARTs for their targets. A combination of different technological approaches reveals that ecto-ARTs are expressed in different tissues with privileged sites such as heart and skeletal muscles for ART1, T lymphocytes for ART2 or testis for ART5. It also indicates that ART expression is highly regulated. ADP-ribosylation of target proteins on cell surfaces or circulating in body fluids leads to reversible post-translational modifications which can inhibit the targets, as known for bacterial ARTs, or activate them, as in the crosstalk between mouse ART2 and the cytolytic P2X7 receptor on T lymphocytes. ART activity in the extracellular compartment provides sophisticated regulatory mechanisms for cell communication. This designates ecto-ARTs as new candidates for drug targeting.


Association between self-perceived pain sensitivity and pain intensity after cardiac surgery.
Cardiac surgical pain remains a clinical challenge affecting about 40% of individuals in the first six months post-cardiac surgery, and continues up to two years after surgery for about 15-20%. Self-perceived sensitivity to pain may help to identify individuals at risk for persistent cardiac surgical pain to optimize health care responses. The purpose of this study was to assess the relationship between self-perceived pain sensitivity assessed by the Pain Sensitivity Questionnaire (PSQ) and postoperative worst pain intensity up to 12 months after cardiac surgery. Sex differences in baseline characteristics and the PSQ scores were also assessed. This study was performed among 416 individuals (23% women) scheduled for elective coronary artery bypass graft and/or valve surgery between March 2012 and September 2013. A secondary data-analysis was utilized to explore the relationship between preoperative PSQ scores and worst pain intensity rated preoperatively, across postoperative Days 1-4, at 2 weeks, and at 1, 3, 6, and 12 months post-surgery. Linear mixed model analyses were performed to estimate changes in pain intensity during 1-year follow-up. The mean (±standard deviation) PSQ-total score was 3.3±1.4, with similar scores in men and women. The PSQ-total score was significantly associated with higher worst pain intensity ratings adjusted for participant characteristics (p=0.001). Use of the PSQ before surgery may predict cardiac surgical pain intensity. However, previous evidence is limited and not consistent, and more research is needed to substantiate our results.


Characterization of tGLP-1, a Golgi and lysosome-associated, transmembrane glycoprotein of African trypanosomes.
Purification of endosomal/lysosomal vesicles of Trypanosoma brucei brucei bloodstream forms and generation of monoclonal antibodies led to the isolation of antibodies directed against an 85 kDa, Golgi and endocytic traffic-associated protein termed tGLP-1, Trypanosoma Golgi/lysosome protein-1. Preliminary immunoelectron microscopical analysis revealed that the protein is present in, but not restricted to, the limiting membrane of multivesicular lysosomes and is more abundant in bloodstream forms compared to the procyclic stage. The corresponding gene was cloned and is present as a single copy. Blast searches did not reveal any homologies to other proteins and genes published. The nucleotide sequence of the gene (1848 base pairs) predicted a type 1 membrane topology with an N-terminal signal sequence (20 aa), a luminal domain with 2 N-glycosylation sites (524 aa), a transmembrane domain (23 aa), and a long cytosolic tail domain (49 aa). Polyclonal antibodies raised against the cytosolic tail confirmed the localization of the gene product to multivesicular lysosomes but revealed that the majority of the protein was in the Golgi apparatus. Colabelling with an antibody against p67, a lysosomal glycoprotein of trypanosomes, revealed extensive overlap between the proteins with opposing relative abundance. Expression of the tGLP-1 open reading frame in Leishmania resulted in Golgi localization, and in Toxoplasma, in localization to both the Golgi and endoplasmic reticulum. These data indicate conservation in the functionality of the Golgi-targeting sequence of tGLP-1.


Sulfonate-grafted porous polymer networks for preferential CO2 adsorption at low pressure.
A porous polymer network (PPN) grafted with sulfonic acid (PPN-6-SO(3)H) and its lithium salt (PPN-6-SO(3)Li) exhibit significant increases in isosteric heats of CO(2) adsorption and CO(2)-uptake capacities. IAST calculations using single-component-isotherm data and a 15/85 CO(2)/N(2) ratio at 295 K and 1 bar revealed that the sulfonate-grafted PPN-6 networks show exceptionally high adsorption selectivity for CO(2) over N(2) (155 and 414 for PPN-6-SO(3)H and PPN-6-SO(3)Li, respectively). Since these PPNs also possess ultrahigh physicochemical stability, practical applications in postcombustion capture of CO(2) lie well within the realm of possibility.


Photodermatitis in a woman with infiltrating intraductal breast carcinoma: An uncommon adverse cutaneous drug reaction of paclitaxel revisited.
Paclitaxel-induced photodermatitis is extremely rare despite the frequent use of paclitaxel-trastuzumab combination chemotherapy. A 70-year-old woman with infiltrating intraductal breast cancer developed photodermatitis after ten treatment courses of weekly paclitaxel-trastuzumab combination chemotherapy. Withdrawal of paclitaxel and sun avoidance led to its resolution. A combined effect of solar radiation and enhanced porphyrin synthesis is speculated for photodermatitis in paclitaxel. However, the issue of aberrant porphyrin biosynthesis being causal or an epiphenomenon remains unsettled as elevated porphyrins synthesis does not necessarily cause photosensitivity in all treated cases. The relevant literature on paclitaxel-induced photodermatitis and pathomechanism involved is reviewed.


Interleukin-33 has the protective effect on oligodendrocytes against impairment induced by cuprizone intoxication.
Our prior investigations have demonstrated the pivotal role of IL-33 in facilitating the maturation of oligodendrocytes (OLs), prompting our interest in exploring its potential therapeutic effects. In this study, our focus was directed towards deciphering the functions of interleukin-33 (IL-33) in established demyelinating mouse model induced by the feeding of cuprizone (CPZ)-containing diet. We observed the reduction in corpus callosal adenomatous polyposis coli (APC)+ OLs with IL-33 expression in mice subjected to CPZ feeding for durations of 6 and 8 weeks. In parallel, the levels of IL-33 in the corpus callosum declined after CPZ-containing diet. Furthermore, we conducted experiments utilizing primary oligodendrocyte precursor cells (OPCs) and mature OLs, which were exposed to CPZ. A decrease in the expression of myelin basic protein (MBP) was evident in the cultures of mature OLs after treatment with CPZ. Additionally, both IL-33 mRNA and protein levels exhibited downregulation. To counteract the diminished IL-33 levels induced by CPZ, we employed a lentiviral vector to overexpress IL-33 in OLs. Intriguingly, the overexpression of IL-33 (IL33OE) in OLs resulted in a more distinct membranous morphology following CPZ treatment when compared to that observed in OL Mock cultures. Moreover, MBP protein levels in the presence of CPZ were higher in IL33OE OLs than that detected in OL Mock cultures. These findings collectively indicate that IL-33 possesses the capability to mitigate CPZ-induced damage and bolster OL homeostasis. In summary, our study underscores the importance of IL-33 in the context of demyelinating diseases, shedding light on its potential therapeutic implications for fostering remyelination and preserving OL function.


Representations of the veterinary profession in nonfiction children's books.
To evaluate how the veterinary profession is represented in nonfiction children's books and determine whether representations reflect the current veterinary profession or the demographics of the United States. Survey. Covers of 46 nonfiction children's books and contents of 45 nonfiction children's books. Book covers and book contents (images and text) were evaluated for representations of veterinarians and to identify settings, clients, technology and equipment, and animals portrayed. Book contents were additionally evaluated to identify specialties and career opportunities specifically mentioned in the text. Book covers predominantly portrayed veterinarians as Caucasian women who wore examination coats, worked alone in veterinary clinics, and cared for dogs without a client present. Book contents predominantly portrayed veterinarians as a Caucasian man or woman who wore an examination coat, worked as part of a team in a veterinary clinic, and helped clients care for dogs, cats, and exotic animals. Specialties and career opportunities in the veterinary profession were mentioned in the text of 29 of 45 (64.4%) books. Nonfiction children's book covers that focused on the veterinary profession portrayed a greater percentage of women than is currently found in the profession. Similarly, books portrayed a greater percentage of Caucasians than in the current or predicted US population. With the exception of Asians, books collectively represented lower or similar percentages of underrepresented minorities, compared with the US population. Veterinarians are encouraged to select books for individual children that portray veterinarians with whom the children can identify.


2010 topical meeting on optical interference coatings: manufacturing problem.
For the 2010 Manufacturing Problem, the participants were required to produce a filter that had normal incidence transmittances of 0.001, 0.01, 0.1, and 0.96, respectively, in four separate 60 nm wide bands in the 400 to 700 nm wavelength region. The problem is not unlike those that need to be routinely solved in the telecommunication industry. Nine groups submitted a total of 11 different filters for the contest. The number of layers in the filters received ranged from 28 to 678, and the total metric thicknesses varied between 4,038 and 22,513 nm. The transmittances of the filters were measured at two independent laboratories. Some of the performances were quite close to the specifications.


No change in the incidence of ampicillin-resistant, neonatal, early-onset sepsis over 18 years.
The objective of this study was to assess the effect of maternal antibiotic exposure on neonatal early-onset sepsis (EOS) rates over an 18-year period. A review was performed of infant and maternal records for all culture- proven cases of EOS in infants delivered at the Brigham and Women's Hospital (Boston, MA) in 1990-2007. Data were analyzed from 335 EOS cases over periods that differed with respect to hospital policy for intrapartum antibiotic prophylaxis against group B Streptococcus (GBS): 1990-1992 (no prophylaxis); 1993-1996 (risk-based); and 1997-2007 (screening-based). The overall incidence of EOS decreased over these periods (3.70 vs 2.23 vs 1.59 cases per 1000 live births; P < .0001). No change in the incidence of infection with ampicillin-resistant organisms was observed overall or among very low birth weight infants. However, an increased proportion of infections were caused by ampicillin- resistant organisms. Mothers of infants with ampicillin-resistant infections were more likely to have been treated with ampicillin (P = .0001). Overall peripartum antibiotic use increased during the study period primarily because of increased use of penicillin G and clindamycin, with no significant change in the use of ampicillin. Predominant use of penicillin G for GBS prophylaxis resulted in decreased incidence of EOS. No change in the incidence of ampicillin-resistant EOS was observed, but resistant cases were associated with peripartum ampicillin exposure. These findings suggest that obstetricians should consider preferential use of penicillin G for GBS prophylaxis.


[Abdominal pregnancy. Surgical emergency].
Concept, classification, frequency and predominant factors of abdominal pregnancy, were reviewed. The case of a patient 32 years old, from Hospital General Tacuba, ISSSTE; with a history of secondary sterility of seven years duration, win an abdominal pregnancy with symptomatology mainly digestive; she was under hypovolemic shock, acute abdomen, but with an ultrasonographic study showing intrauterine pregnancy and a tumor in right iliac fossa, which confounded the preoperative diagnosis. Exploratory laparotomy, was done. An alive product was found 14 to 16 years old, and living the placenta in situ. Evolutions was favorable. In the final comment the clinical picture, the diagnostic media, the management possibilities for the placenta and hemorrhage, are mentioned.


A current perspective on daptomycin for the clinical microbiologist.
Daptomycin is a lipopeptide antimicrobial with in vitro bactericidal activity against Gram-positive bacteria that was first approved for clinical use in 2004 in the United States. Since this time, significant data have emerged regarding the use of daptomycin for the treatment of serious infections, such as bacteremia and endocarditis, caused by Gram-positive pathogens. However, there are also increasing reports of daptomycin nonsusceptibility, in Staphylococcus aureus and, in particular, Enterococcus faecium and Enterococcus faecalis. Such nonsusceptibility is largely in the context of prolonged treatment courses and infections with high bacterial burdens, but it may occur in the absence of prior daptomycin exposure. Nonsusceptibility in both S. aureus and Enterococcus is mediated by adaptations to cell wall homeostasis and membrane phospholipid metabolism. This review summarizes the data on daptomycin, including daptomycin's unique mode of action and spectrum of activity and mechanisms for nonsusceptibility in key pathogens, including S. aureus, E. faecium, and E. faecalis. The challenges faced by the clinical laboratory in obtaining accurate susceptibility results and reporting daptomycin MICs are also discussed.


Central diabetes insipidus in children and young adults.
Central diabetes insipidus is rare in children and young adults, and up to 50 percent of cases are idiopathic. The clinical presentation and the long-term course of this disorder are largely undefined. We studied all 79 patients with central diabetes insipidus who were seen at four pediatric endocrinology units between 1970 and 1996. There were 37 male and 42 female patients whose median age at diagnosis was 7.0 years (range, 0.1 to 24.8). All patients underwent magnetic resonance imaging (MRI) and periodic studies of anterior pituitary function. The median duration of follow-up was 7.6 years (range, 1.6 to 26.2). The causes of the central diabetes insipidus were Langerhans-cell histiocytosis in 12 patients, an intracranial tumor in 18 patients, a skull fracture in 2 patients, and autoimmune polyendocrinopathy in 1 patient; 5 patients had familial disease. The cause was considered to be idiopathic in 41 patients (52 percent). In 74 patients (94 percent) the posterior pituitary was not hyperintense on the first MRI scan obtained, and 29 patients (37 percent) had thickening of the pituitary stalk. Eighteen patients had changes in the thickness of the pituitary stalk over time, ranging from normalization (six patients) or a decrease in thickness (one patient) to further thickening (seven patients) or thickening of a previously normal stalk (four patients). Anterior pituitary hormone deficiencies, primarily growth hormone deficiency, were documented in 48 patients (61 percent) a median of 0.6 year (range, 0.1 to 18.0) after the onset of central diabetes insipidus. Most children and young adults with acquired central diabetes insipidus have abnormal findings on MRI scans of the head, which may change over time, and at least half have anterior pituitary hormone deficiencies during follow-up.


Predicting West Nile virus transmission in North American bird communities using phylogenetic mixed effects models and eBird citizen science data.
West Nile virus (WNV) is a mosquito-transmitted disease of birds that has caused bird population declines and can spill over into human populations. Previous research has identified bird species that infect a large fraction of the total pool of infected mosquitoes and correlate with human infection risk; however, these analyses cover small spatial regions and cannot be used to predict transmission in bird communities in which these species are rare or absent. Here we present a mechanistic model for WNV transmission that predicts WNV spread (R0) in any bird community in North America by scaling up from the physiological responses of individual birds to transmission at the level of the community. We predict unmeasured bird species' responses to infection using phylogenetic imputation, based on these species' phylogenetic relationships with bird species with measured responses. We focused our analysis on Texas, USA, because it is among the states with the highest total incidence of WNV in humans and is well sampled by birders in the eBird database. Spatio-temporal patterns: WNV transmission is primarily driven by temperature variation across time and space, and secondarily by bird community composition. In Texas, we predicted WNV R0 to be highest in the spring and fall when temperatures maximize the product of mosquito transmission and survival probabilities. In the most favorable months for WNV transmission (April, May, September and October), we predicted R0 to be highest in the "Piney Woods" and "Oak Woods & Prairies" ecoregions of Texas, and lowest in the "High Plains" and "South Texas Brush County" ecoregions. Dilution effect: More abundant bird species are more competent hosts for WNV, and predicted WNV R0 decreases with increasing species richness. Keystone species: We predicted that northern cardinals (Cardinalis cardinalis) are the most important hosts for amplifying WNV and that mourning doves (Zenaida macroura) are the most important sinks of infection across Texas. Despite some data limitations, we demonstrate the power of phylogenetic imputation in predicting disease transmission in heterogeneous host communities. Our mechanistic modeling framework shows promise both for assisting future analyses on transmission and spillover in heterogeneous multispecies pathogen systems and for improving model transparency by clarifying assumptions, choices and shortcomings in complex ecological analyses.


Interventions for ulceration and other skin changes caused by nerve damage in leprosy.
At the end of 2016, 145 countries reported to the World Health Organization (WHO) over 173,000 new cases of leprosy worldwide. In the past 20 years, over 16 million people have been treated for leprosy globally. The condition's main complications are injuries and ulceration caused by sensory loss from nerve damage. In this review we explored interventions to prevent or treat secondary damage to the skin in people affected by leprosy (Hansen's disease). This is an update of a Cochrane Review published in 2008. To assess the effects of education, information, self-care programmes, dressings, skin care, footwear and other measures for preventing and healing secondary damage to the skin in persons affected by leprosy. We updated our searches of the following databases up to July 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, and CINAHL. We also searched five trial registers, three grey literature databases, and the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). RCTs or quasi-RCTs or randomised cross-over trials involving anyone with leprosy and potential damage to peripheral nerves who was treated with any intervention designed to prevent damage, heal existing ulcers, and prevent development of new ulcers. Eligible comparisons were usual care, no interventions, or other interventions (e.g. other types of dressings or footwear). We adhered to standard methodological procedures expected by Cochrane. Primary outcomes were prevention of ulcer(s), healing of existing ulcer(s) and adverse events. We used GRADE to assess the certainty of evidence for each outcome. We included 14 trials (854 participants). Eleven studies reported on gender (men: 472, women: 157). Participant age varied from 18 to 74 years. Most participants had a single, mainly non-infected, wound on one foot, which had been there for less than a year. Only seven studies reported whole study duration (there was no follow-up post-treatment), which was on average six months (range: 1 to 12 months). The studies were conducted in Brazil, Ethiopia, Egypt, Indonesia, Mexico, South Korea, and India. Many 'Risk of bias' assessments were rated as unclear risk due to limited information. Six studies had high risk of bias in at least one domain, including selection and attrition bias.Thirteen studies evaluated different interventions for treating existing ulcers, one of them also evaluated prevention of new ulcers. One study aimed to prevent skin changes, such as cracking and fissures. Investigated interventions included: laser therapy, light-emitting diode (LED), zinc tape, intralesional pentoxifylline, pulsed magnetic fields, wax therapy, ketanserin, human amniotic membrane gel, phenytoin, plaster shoes, and footwear.We are uncertain about the following key results, as the certainty of evidence is very low. All time points were measured from baseline.Three studies compared zinc tape versus other interventions and reported results in favour of zinc tape. One study compared zinc tape versus magnesium sulphate: at one month the number of healed ulcers and reduction in mean ulcer area was higher with zinc tape (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.43 to 9.21, and mean difference (MD) -14.30 mm², 95% CI -26.51 to -2.09, respectively, 28 participants). Another study compared zinc tape and povidone iodine and found that even though there was a greater reduction in ulcer area after six weeks of treatment with zinc tape, there was no clear difference due to the wide 95% CI (MD 128.00 mm², 95% CI -110.01 to 366.01; 38 participants). The third study (90 participants) compared adhesive zinc tape with gauze soaked in Eusol, and found the healing time for deep ulcers was less compared to zinc tape: 17 days (95% CI 12 to 20) versus 30 days (95% CI 21 to 63). Adverse events were only collected in the study comparing zinc tape with gauze soaked in Eusol: there were no signs of skin sensitisation in either group at two months.Two studies compared topical phenytoin versus saline dressing and reported results in favour of phenytoin. One study reported a greater mean percentage reduction of ulcer area after four weeks with phenytoin 2% (MD 39.30%, 95% CI 25.82 to 52.78; 23 participants), and the other study reported a greater mean percentage reduction of ulcer volume (16.60%) after four weeks with phenytoin (95% CI 8.46 to 24.74; 100 participants). No adverse events were observed with either treatment during the four-month treatment period (2 studies, 123 participants). Prevention of ulcers was not evaluated in these nor the zinc studies, as the interventions were not for preventative use.Two studies compared protective footwear (with or without self-care) with either 1) polyvinyl chloride (PVC) boots, or 2) pulsed magnetic fields plus self-care and protective footwear. In the study comparing canvas shoes versus PVC boots, none of the 72 participants with scars at the start of the study developed new ulcers over one-year follow-up. Healing of ulcers was assessed in 38 participants from this study, but we are unclear if there is a difference between groups. In the study comparing pulsed magnetic fields (in addition to self-care and protective footwear) to only self-care and footwear in 33 participants, we are uncertain if the mean volume of ulcers at four to five weeks' follow-up was different between groups; this study did not evaluate the prevention of ulcers. Information for adverse events was only reported in the study comparing canvas shoes with PVC boots; the authors stated that the PVC boots could become hot in strong sunlight and possibly burn the feet. Based on the available evidence, we could not draw firm conclusions about the effects of the included interventions. The main evidence limitations were high or unclear risk of bias, including selection, performance, detection, and attrition bias; imprecision due to few participants in the studies; and indirectness from poor outcome measurement and inapplicable interventions. Future research should clearly report important outcomes, such as adverse events, and assess widely available interventions, which should include treatments aimed at prevention. These trials should ensure allocation concealment, blinding, and an adequate sample size.


Morphological and biochemical studies of canine progressive rod-cone degeneration. 3H-fucose autoradiography.
Visual cell pathology and rod outer segment renewal were investigated in normal and PRCD-affected miniature poodles using 3H-fucose autoradiography. Twenty-four hours following the intravitreal injection of 3H-fucose, label accumulated diffusely over cone OS and in a banded pattern at the rod OS base. In normal rods, the band of 3H-label was displaced sclerad with time. PRCD-affected rods in the early stages of the disease (stages 0-1) also showed a similar 3H-label pattern but a significantly (P less than 0.001) reduced renewal rate (control = 2.35 +/- 0.43 mu/24 hr; affected = 0.99 +/- mu/24 hr). This abnormal renewal rate was present in central, equatorial, and peripheral visual cells and was not associated with the presence or density of pigment in the RPE cell layer. Biochemical studies indicated that the 3H-label was present as an integral membrane component in the rod OS and confirmed that canine rhodopsin is a fucosylated glycoprotein. The 3H-band in the rod OS layer disappeared in stage 2 of the disease; diffuse label now was present over rod OS that had decreased length and were reduced in number. At this stage of the disease, interphotoreceptor space was invaded by phagocytic cells, and photoreceptor nuclei were lost from the outer nuclear layer. These late degenerative changes were more extensive in the superior and inferior retinal meridians.


The place of renal scintigraphy in the diagnosis of renal artery stenosis. Fifteen years of clinical experience.
Renal scintigraphy with radiolabeled pentetic acid (diethylenetriamine pentaacetic acid [DTPA]) or, more recently, mertiatide (mercaptoacetyltriglycine [MAG3]), with or without captopril challenge, is widely recommended as a diagnostic test for renal artery stenosis. To address (1) whether the diagnostic accuracy has been improved by the use of captopril and the introduction of mertiatide and (2) whether a renal scan that shows abnormalities is a useful criterion to select patients for renal arteriography. A standard diagnostic protocol, using both scintigraphy and arteriography, was followed in 505 consecutive high-risk hypertensive patients who were evaluated for renovascular hypertension at the University Hospital Dijkzigt, Rotterdam, the Netherlands, from 1978 to 1992. Renal artery stenosis (> or = 50%) was present in 263 patients. When the single-kidney fractional uptake was used as a diagnostic criterion, a specificity of 0.90 was obtained at a cutoff value of 35% for the worst kidney in scintigraphy using pentetic acid without captopril challenge (n = 225) and at a cutoff value of 37% after captopril challenge (n = 280). This was associated with sensitivity levels of 0.65 and 0.68, respectively. The difference between the uptake of pentetic acid with and without captopril challenge in the 85 patients who were studied under both circumstances was no more accurate as a predictor of renal artery stenosis. In the 93 patients who were studied with mertiatide as well as with pentetic acid, both after captopril challenge, the diagnostic accuracy was no better with mertiatide than with pentetic acid; mertiatide failed to offer any advantage not only when the single-kidney fractional uptake was used as a criterion, but also with the use of other scintigraphic parameters (eg, time to peak, time to pyelum, overall shape of renographic curve, and kidney size). The diagnostic accuracy of renal scintigraphy has not been improved by the introduction of mertiatide or by the use of captopril. The usefulness of scintigraphy as a diagnostic test for the presence of renal artery stenosis remains questionable. The physician will always confront either a substantial number of arteriograms that do not show abnormalities when renal scintigraphy is omitted as a screening step or a substantial number of missed diagnoses when a renal scan that shows abnormalities is used as a prerequisite for arteriography.


Reducing Falls Among Community-Dwelling Older Adults From Clinicians' Perspectives: A Systems Modeling Approach.
Falls among older adults are a significant health problem globally. Studies of multicomponent fall prevention programs in randomized controlled trials demonstrate effectiveness in reducing falls; however, the translation of research into the community remains challenging. Although there is an increasing interest to understand the factors contributing to implementation barriers, the dynamic relationships between factors are less well examined. Furthermore, evidence on implementation barriers from Asia is lacking as most of these studies originate from the West. As such, this study aims to engage stakeholders in uncovering the factors that facilitate or inhibit implementing community-based fall prevention programs in Singapore, with a focus on the interrelationship between those factors. Health care professionals familiar with fall prevention programs were invited to discuss the enablers and challenges to the implementation. This effort was facilitated using a systems modeling methodology of Group Model Building (GMB) to share ideas and create a common conceptual model of the challenges. The GMB employs various engagement techniques to draw on the experiences and perceptions of all stakeholders involved. This process led to the development of a Causal Loop Diagram (CLD), a qualitative conceptual model of the dynamic relationships between the barriers and facilitators of implementing fall prevention programs. Results from the CLD show that implementation is influenced by two main drivers: health care provider factors that influenced referrals, and patient factors that influenced referral acceptance and long-term adherence. Key leverage points for potential interventions were identified as well. The overall recommendation emphasized closer coordination and collaboration across providers to ensure sustainable and effective community-based fall prevention programs. This has to be supported by a national effort, involving a multidisciplinary stakeholder advisory group. These findings generated would be promising to guide future approaches to fall prevention.


The opportunities and challenges of large-scale molecular approaches to songbird neurobiology.
High-throughput methods for analyzing genome structure and function are having a large impact in songbird neurobiology. Methods include genome sequencing and annotation, comparative genomics, DNA microarrays and transcriptomics, and the development of a brain atlas of gene expression. Key emerging findings include the identification of complex transcriptional programs active during singing, the robust brain expression of non-coding RNAs, evidence of profound variations in gene expression across brain regions, and the identification of molecular specializations within song production and learning circuits. Current challenges include the statistical analysis of large datasets, effective genome curations, the efficient localization of gene expression changes to specific neuronal circuits and cells, and the dissection of behavioral and environmental factors that influence brain gene expression. The field requires efficient methods for comparisons with organisms like chicken, which offer important anatomical, functional and behavioral contrasts. As sequencing costs plummet, opportunities emerge for comparative approaches that may help reveal evolutionary transitions contributing to vocal learning, social behavior and other properties that make songbirds such compelling research subjects.


Means, motive and opportunity for biological invasions: Genetic introgression in a fungal pathogen.
Invasions by fungal plant pathogens pose a significant threat to the health of agricultural ecosystems. Despite limited standing genetic variation, many invasive fungal species can adapt and spread rapidly, resulting in significant losses to crop yields. Here, we report on the population genomics of Colletotrichum truncatum, a polyphagous pathogen that can infect more than 460 plant species, and an invasive pathogen of soybean in Brazil. We study the whole-genome sequences of 18 isolates representing 10 fields from two major regions of soybean production. We show that Brazilian C. truncatum is subdivided into three phylogenetically distinct lineages that exchange genetic variation through hybridization. Introgression affects 2%-30% of the nucleotides of genomes and varies widely between the lineages. We find that introgressed regions comprise secreted protein-encoding genes, suggesting possible co-evolutionary targets for selection in those regions. We highlight the inherent vulnerability of genetically uniform crops in the agro-ecological environment, particularly when faced with pathogens that can take full advantage of the opportunities offered by an increasingly globalized world. Finally, we discuss "the means, motive and opportunity" of fungal pathogens and how they can become invasive species of crops. We call for more population genomic studies because such analyses can help identify geographical areas and pathogens that pose a risk, thereby helping to inform control strategies to better protect crops in the future.


Vernakalant--a promising therapy for conversion of recent-onset atrial fibrillation.
This paper reviews the pharmacology, electrophysiology, efficacy and safety of intravenous and oral vernakalant hydrochloride (RSD-1235), a novel antiarrhythmic drug that has relative atrial selectivity by blocking potassium channels that are present in the atria and not the ventricle. In addition, this drug has important rate-dependent sodium channel blocking properties. Currently, there few commercially approved intravenous antiarrhythmic agents for the conversion of atrial fibrillation. Intravenously, vernakalant has been demonstrated to be useful in terminating over 50% of recent-onset atrial fibrillation (< 7 days duration) with minimal ventricular proarrhythmic effects. Intravenous vernakalant is not effective in terminating atrial flutter. Oral vernakalant is currently undergoing study and appears to be effective in suppressing atrial fibrillation recurrences after cardioversion of persistent atrial fibrillation. Intravenous vernakalant has the potential to be an important agent in the conversion of atrial fibrillation and oral vernakalant may be a useful drug for the suppression of atrial fibrillation recurrences.


Comparative evaluation of the BD Phoenix and VITEK 2 automated instruments for identification of isolates of the Burkholderia cepacia complex.
We evaluated two new automated identification systems, the BD Phoenix (Becton Dickinson) and the VITEK 2 (bioMérieux), for identification of isolates of the Burkholderia cepacia complex (BCC). The test sample included 42 isolates of the highly virulent and epidemic genomovar III, 45 isolates of B. multivorans, and 47 isolates of other members of the BCC. Rates of correct identification by the BD Phoenix and VITEK 2 were similar when all BCC isolates were considered (50 and 53%, respectively) but differed markedly for genomovar III (71 and 38%; P < 0.01) and for B. multivorans (58 and 89%; P < 0.001). For the BD Phoenix as well as the VITEK 2, taking all 134 isolates of the BCC together, rates of correct identification of clinical isolates (56 and 55%, respectively; n = 85) were higher than those of environmental isolates (21 and 39%, respectively; n = 28). Clinical isolates of genomovar III (n = 27) showed correct identification rates of 81% (BD Phoenix) and 48% (VITEK 2) (P < 0.01). Rates of misidentification for BD Phoenix and VITEK 2 were 9 and 17% for genomovar III, 22 and 7% for B. multivorans, and 36 and 13% for the other BCC members (P < 0.01), respectively. More than half of the isolates misidentified by each instrument were identified as Ralstonia pickettii, Ralstonia paucula (CDC IV C-2 group), Alcaligenes faecalis, Achromobacter spp., or, for the VITEK 2, "various nonfermenters." This study reemphasizes that confirmatory identification of BCC, preferably by molecular methods, is highly recommended.


Improvement of cocktail tomato yield and consumer-oriented quality traits by potassium fertilization is driven by the cultivar.
The market for cocktail tomatoes is growing continuously, mainly because of their good taste. Titratable acids (TA), total soluble solids (TSS) and dry matter (DM) contents correlate positively with good taste. So far, the impact of different potassium (K) applications on yield and consumer-oriented quality traits has not been comprehensively described for cultivars of smaller fruits. To fill this gap, we tested the effect of different K fertilization regimes on three cultivars of small-sized or cocktail tomatoes. A positive impact on quality parameters (TSS, TA, DM, color and firmness) was detected by raising the K fertilizer application for the cocktail tomato cultivars Primavera and Yellow Submarine. The cultivar Resi showed no response to fertilization, except for TSS and TA. Yield increased significantly by higher K application only in Primavera, the most productive cultivar. The K concentration in tomato rose with increasing K application. Because TSS and TA increased in all cultivars, whereas only one cultivar showed an increase in yield, the results of the present study emphasize the importance of the application of cultivar-specific mineral fertilizers on yield- and consumer-oriented quality traits. © 2018 Society of Chemical Industry.


Mutation Lys758 --> Ile of the sarcoplasmic reticulum Ca2+-ATPase enhances dephosphorylation of E2P and inhibits the E2 to E1Ca2 transition.
The highly conserved lysine residue Lys758 in the fifth stalk segment of the sarcoplasmic reticulum Ca2+-ATPase was substituted with either isoleucine or arginine by site-directed mutagenesis. The substitution with arginine was without significant effects on Ca2+-ATPase function, whereas multiple changes of functional characteristics were observed with the Lys758 --> Ile mutant. These included insensitivity of ATPase activity to the calcium ionophore A23187, an alkaline shift of the pH dependence of ATPase activity, reduced maximum molecular turnover rate and steady-state phosphorylation level, reduced apparent affinities for Ca2+ and inorganic phosphate, as well as increased sensitivity to inhibition by vanadate. Analysis of the partial reaction steps of the enzyme cycle traced these changes to two steps. The rate of dephosphorylation of the ADP-insensitive phosphoenzyme intermediate (E2P) was increased, irrespective of variations of pH, K+, Ca2+, and dimethyl sulfoxide concentration. In addition, the rate of conversion of the dephosphoenzyme with low Ca2+ affinity (E2) to the Ca2+-bound form activated for phosphorylation (E1Ca2) was reduced in the mutant, and the ATP-induced rate enhancement of this step required higher ATP concentrations in the mutant compared with the wild type.


"Counting Carbs to Be in Charge": A Comparison of an Internet-Based Education Module With In-Class Education in Adolescents With Type 1 Diabetes.
Carbohydrate counting is an essential component of type 1 diabetes education but can be difficult for adolescents to learn. Because adolescents are avid users of technology, an Internet-based education module was compared with an in-class education session in terms of carbohydrate counting accuracy in adolescents with type 1 diabetes. Adolescent participants displayed increased carbohydrate counting accuracy after attending an in-class education session compared with an Internet-based education module. These results suggest that online education is best reserved as an adjunctive therapy to in-class teaching in this population.


Two-way reaction of versatile peroxidase with artificial lignin enhances low-molecular weight fractions.
In recent years, versatile peroxidase (VP) has emerged as a promising enzyme for biotechnological applications, as it can oxidize lignin without the external mediators. To gain insights into the breakdown process of artificial lignin by VP, reaction between the two was studied. Degradation products were fractionated using ultrafiltration and analyzed by RP- high performance liquid chromatography with mass detection (HPLC-MS) chromatography. Four fractions were obtained based on their molecular sizes: >10, 3-10, 1-3, and <1 kDa. Interestingly, while VP did not significantly alter the yields of these fractions, the chromatograms revealed the presence of oligomers with different molecular weights (MWs) resulting from the enzymatic activity. The VP exhibits a dual role in its enzymatic activity: both degrading and synthesizing these oligomers. This was confirmed by principal component analysis (PCA). The positive correlations were found between certain oligomers (D1 and D2, D5 and D6, as well as between D7, D10, T2, and T4), suggesting their simultaneous degradation. On the other hand, a negative correlation was found between the monomer and some oligomers (D7, D10, T2, and T4), indicating the decomposition of these oligomers into monomers. These findings shed light on the intricate interplay between VP and artificial lignin, offering valuable insights for potential applications in lignin valorization.


Nonmodifiable factors and complications contribute to length of stay in robot-assisted partial nephrectomy.
Robotic-assisted partial nephrectomy (RPN) offers a mean length of stay (LOS) of 2 to 3 days. The purpose of this study is to determine the impact of modifiable and nonmodifiable risk factors on hospital LOS after RPN. We retrospectively reviewed our prospectively maintained database to identify all patients undergoing RPN for localized tumors at five US centers from 2007 to 2013. Patient and tumor characteristics were compared among hospital LOS groups. Associated factors were modeled using univariate and multivariate cumulative logistic regression to determine factors predictive of hospital LOS. One thousand five hundred thirty-two patients were grouped into LOS 1 to 3 days (1298, 84.1%), LOS=4 days (133, 8.6%), and LOS >4 days (110, 7.2%). Patient demographics were similar between groups. Patients in the LOS=4 and LOS >4 day groups were more likely to have a higher Charlson comorbidity index score (mean 2.2, 3.1 and 3.8; p<0.001), higher nephrometry score (mean 7.1, 7.6, 7.8; p=0.0002), and larger tumors (mean 2.9, 3.6 and 3.5 cm; p<0.0001) than those in the LOS 1 to 3 day group. Significant differences in complication rates were observed when comparing LOS 1-3 (116, 8.9%), LOS=4 (40, 30%), and LOS >4 (59, 54%). According to the Clavien-Dindo classification of surgical complications, 11 grade 3 and 11 grade 4 complications occurred in patients with an LOS of 4 or more days (p<0.0001). Postoperative transfusion, deep vein thrombosis, pulmonary embolism, atrial fibrillation, dyspnea/atelectasis, ileus, and acute renal failure each significantly predicted a hospital LOS >4 days (p<0.001). 15.8% of patients undergoing RPN have an LOS of 4 days or more. Longer LOS was independently associated with higher Charlson index, nephrometry score (nonmodifiable factors), and perioperative complications (potentially modifiable). These data may be useful in perioperative counseling and payer precertification.


Conditional release and cannabis use: Concerns and challenges for community reintegration.
This article, which serves as a perspective review, delves into the complexities of cannabis use among individuals preparing for or already on conditional release (CR). These complexities include an association between cannabis use and mental illness and dealing with the fact that the use of illicit substances, such as cannabis, is against CR rules, leading to potential revocation. A focus of this article is the deleterious effects cannabis and synthetic derivatives of cannabis can have for individuals on CR. The article concludes with six-specific recommendations for managing cannabis use in this population with a focus on careful and detailed risk assessments that considers the relationship between substance use and dangerousness, the role of protective factors, the need for a detailed conditional release plan, inpatient and community-based interventions aimed at increasing individual autonomy, and education on the dangers of cannabis use for both the treatment team and the insanity acquittee.


Modulation of endoplasmic reticulum stress and cardiomyocyte apoptosis by mulberry leaf diet in experimental autoimmune myocarditis rats.
Mulberry is commonly used as silkworm diet and an alternative medicine in Japan and China, has recently reported to contain many antioxidative flavanoid compounds and having the free radical scavenging effects. Antioxidants reduce cardiac oxidative stress and attenuate cardiac dysfunction in animals with pacing-induced congestive heart failure. Hence we investigated the cardioprotective effect of mulberry leaf powder in rats with experimental autoimmune myocarditis. Eight-week-old Lewis rats immunized with cardiac myosin were fed with either normal chow or a diet containing 5% mulberry leaf powder and were examined on day 21. ML significantly decreased oxidative stress, myocyte apoptosis, cellular infiltration, cardiac fibrosis, mast cell density, myocardial levels of sarco/endo-plasmic reticulum Ca(2+) ATPase2, p22(phox), receptor for advanced glycation end products, phospho-p38 mitogen activated protein kinase, phospho-c-Jun NH(2)-terminal protein kinase, glucose regulated protein78, caspase12 and osteopontin levels in EAM rats. These results may suggest that mulberry diet can preserve the cardiac function in experimental autoimmune myocarditis by modulating oxidative stress induced MAPK activation and further afford protection against endoplasmic reticulum stress mediated apoptosis.


The role of glycogen synthase phosphatase in the glucocorticoid-induced deposition of glycogen in foetal rat liver.
1. The mechanism that underlies the induction of glycogen synthesis in the foetal rat liver by glucocorticoids was reinvestigated in conditions where the accumulation of glycogen is either precociously induced with dexamethasone or inhibited by steroid deprivation. It appears that glucocorticoids act as the physiological trigger for glycogen synthesis by inducing both glycogen synthase (a known effect) and its activating enzyme, glycogen synthase phosphatase. 2. The activity of glycogen synthase phosphatase in adult liver stems from the interaction of two protein components [Doperé, Vanstapel & Stalmans (1980) Eur. J. Biochem. 104, 137--146]. Two independent experimental approaches indicate that the cytosolic 'S-component' is already well developed in the foetal liver before the onset of glycogen synthesis. The manifold glucocorticoid-dependent increase in synthase phosphatase activity during late gestation must be attributed to the specific development of the glycogen-bound 'G-component'.


Vegetative endocarditis in an Appaloosa gelding.
A 5-year-old Appaloosa gelding was presented with a history of intermittent multiple joint swelling, weight loss, and anemia. Physical examination and clinical pathology revealed a grade IV/VI holodiastolic murmur, louder on the left, and a marked hyperproteinemia. Echocardiography of the heart demonstrated a large vegetative lesion on one of the aortic valve cusps. Blood cultures did not elucidate the causative organism, and the disease was refractory to empiric antibiotic therapy. The horse was euthanized after approximately 2 months of therapy.


Sinensetin enhances adipogenesis and lipolysis by increasing cyclic adenosine monophosphate levels in 3T3-L1 adipocytes.
Sinensetin is a rare polymethoxylated flavone (PMF) found in certain citrus fruits. In this study, we investigated the effects of sinensetin on lipid metabolism in 3T3-L1 cells. Sinensetin promoted adipogenesis in 3T3-L1 preadipocytes growing in incomplete differentiation medium, which did not contain 3-isobutyl-1-methylxanthine. Sinensetin up-regulated expression of the adipogenic transcription factors peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein (C/EBP) α, and sterol regulatory element-binding protein 1c. It also potentiated expression of C/EBPβ and activation of cAMP-responsive element-binding protein. Sinensetin enhanced activation of protein kinase A and increased intracellular cAMP levels in 3T3-L1 preadipocytes. In mature 3T3-L1 adipocytes, sinensetin stimulated lipolysis via a cAMP pathway. Taken together, these results suggest that sinensetin enhances adipogenesis and lipolysis by increasing cAMP levels in adipocytes.


Impact of stagnation and sampling volume on water microbial quality monitoring in large buildings.
Microbial drinking water quality can be altered in large buildings, especially after stagnation. In this study, bacterial profiles were generated according to the stagnation time and the volume of water collected at the tap. Successive volumes of cold and hot water were sampled after controlled stagnation periods. Bacterial profiles revealed an important decline (> 2 log) in culturable cells in the first 500 mL sampled from the hot and cold water systems, with a steep decline in the first 15 mL. The strong exponential correlation (R2 ≥ 0.97) between the culturable cell counts in water and the pipe surface-to-volume ratio suggests the biofilm as the main contributor to the rapid increase in suspended culturable cells measured after a short stagnation of one-hour. Results evidence the contribution of the high surface-to-volume ratio at the point of use and the impact of short stagnation times on the increased bacterial load observed. Simple faucets with minimal internal surface area should be preferred to minimize surface area. Sampling protocol, including sampling volume and prior stagnation, was also shown to impact the resulting culturable cell concentration by more than 1000-fold. Sampling a smaller volume on first draw after stagnation will help maximize recovery of bacteria.


[Formula: see text] Reliable change in pediatric brain tumor: A preliminary investigation.
Children treated for brain tumor show evidence of declines in general intellectual abilities (i.e., IQ). Group-level data indicate subtle declines over time on average, but no study has utilized a clinical criterion to identify and describe a reliable change in survivors of pediatric brain tumor (PBT). In this study, we discuss the utility of reliable change index (RCI) methodology to supplement group-level analysis (e.g., repeated measures ANOVA). This pilot sample consisted of 22 children (M age = 10.47 years) treated for PBT who completed initial and follow-up assessments (M interval = 23.58 months). Cognitive data included composite scores from the WISC-IV. An RCI z-score was calculated for each participant on each composite score based on two different test-retest reliability coefficients. As a group, survivors of PBT did not demonstrate a statistically significant change from initial to follow-up on any WISC-IV composite score. When RCI was calculated based on reliability coefficients with shorter test-retest intervals provided by the test publisher, 77% of survivors demonstrated a reliable change in performance on at least one measure. The frequency of RCI decreases in working memory was significantly higher than expected. In contrast, only 32% of survivors showed reliable changes on at least one measure when RCI was based on a reliability coefficient derived from a clinical sample with a longer retest interval. This study demonstrates that highly divergent results may be obtained with RCI and the importance of the source of reliability estimates.


[Plantar pressure distribution in inline skating on straights].
Plantar pressure distribution in inline skating on straight was measured with a flexible insole in 13 experienced subjects at a speed of 18 and 24 km/h. The results showed three areas that were exposed to high pressures, i.e. the heel with 258 and 265 kPa, the first metatarsal head with 265 and 281 kPa, the hallux with 319 and 324 kPa at 18 and 24 km/h, respectively. All other areas showed peak pressures that were less than half of these values. Lowest values were found in the midfoot area. Changing speed from 18 to 24 km/h led to a small increase of peak pressures in all areas. Peak pressures were comparable to walking but showed the trend to be lower than in running.


Nicotine Dependence and Stress Susceptibility in E-Cigarette Smokers: The Korea National Health and Nutrition Examination Survey 2013-2017.
E-cigarettes are steadily gaining popularity in Korea. However, the characteristics of e-cigarette smokers, especially nicotine dependence and stress susceptibility, have not been evaluated in comparison to those of non-smokers or combustible cigarette smokers in Korea. In this study, 28,059 participants from the Korea National Health and Nutrition Examination Survey (2013-2017) were classified into the following three groups: non-smokers, smokers (current smokers and ex-smokers of combustible cigarettes only), and e-smokers (current smokers and ex-smokers of e-cigarettes regardless of combustible cigarette use). Among the participants, 16,980 (60.5%), 9,247 (33.0%), and 1,832 (6.4%) subjects were non-smokers, smokers, and e-smokers, respectively. E-smokers were younger, more educated, and had a higher household income than non-smokers or smokers. The number of e-smokers who smoked within 5 minutes of waking up (31.5% vs. 19.8%, p<0.001) and who planned to quit smoking within 6 months (39.1% vs. 35.7%, p<0.05) was greater than that of smokers. E-smokers perceived stress as "very much" (7.0% vs. 4.4%, p<0.001) and "a lot" (29.1% vs. 20.5%, p<0.001) compared to non-smokers. Suicidal ideation (6.5% vs. 4.7%, p<0.001), plans (2.4% vs. 1.3%, p<0.001), and attempts (1.1% vs. 0.5%, p<0.001) were higher in e-smokers than in non-smokers. Depressive episodes in 1 year (14.2% vs. 11.4%, p<0.05) and suicidal plans (2.4% vs. 1.8%, p<0.05) were more frequent among e-smokers than among smokers. E-smokers were younger, more educated, and had a higher income, but they were more dependent on nicotine and susceptible to stress than non-smokers and smokers. Smoking cessation counseling should be tailored according to the characteristics of e-smokers.


SERS Gas Sensors Based on Multiple Polymer Films with High Design Flexibility for Gas Recognition.
The Surface-Enhanced Raman Scattering (SERS) technique is utilized to fabricate sensors for gas detection due to its rapid detection speed and high sensitivity. However, gases with similar molecular structures are difficult to directly discriminate using SERS gas sensors because there are characteristic peak overlaps in the Raman spectra. Here, we proposed a multiple SERS gas sensor matrix via a spin-coating functional polymer to enhance the gas recognition capability. Poly (acrylic acid) (PAA), Poly (methyl methacrylate) (PMMA) and Polydimethylsiloxane (PDMS) were employed to fabricate the polymer film. The high design flexibility of the two-layer film was realized by the layer-by-layer method with 2 one-layer films. The SERS gas sensor coated by different polymer films showed a distinct affinity to target gases. The principle component analysis (PCA) algorithm was used for the further clustering of gas molecules. Three target gases, phenethyl alcohol, acetophenone and anethole, were perfectly discriminated, as the characteristic variables in the response matrix constructed by the combination of gas responses obtained 3 one-layer and 3 two-layer film-coated sensors. This research provides a new SERS sensing approach for recognizing gases with similar molecular structures.


The consistent labeling problem: part I.
In this first part of a two-part paper we introduce a general consistent labeling problem based on a unit constraint relation T containing N-tuples of units which constrain one another, and a compatibility relation R containing N-tuples of unit-label pairs specifying which N-tuples of units are compatible with which N-tuples of labels. We show that Latin square puzzles, finding N-ary relations, graph or auto-mata homomorphisms, graph colorings, as well as determining satisfiability of propositional logic statements and solving scene and edge labeling problems, are all special cases of the general consistent labeling problem. We then discuss the various approaches that researchers have used to speed up the tree search required to find consistent labelings. Each of these approaches uses a particular look-ahead operator to help eliminate backtracking in the tree search. Finally, we define the ¿KP two-parameter class of look-ahead operators which includes, as special cases, the operators other researchers have used.


Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization.
Polycystic kidney disease (PKD) includes a group of disorders that are characterized by the presence of cysts in the kidney and other organs, including the pancreas. Here we show that in orpk mice, a model system for PKD that harbors a mutation in the gene that encodes the polaris protein, pancreatic defects start to occur at the end of gestation, with an initial expansion of the developing pancreatic ducts. Ductal dilation continues rapidly after birth and results in the formation of large, interconnected cysts. Expansion of pancreatic ducts is accompanied by apoptosis of neighboring acinar cells, whereas endocrine cell differentiation and islet formation appears to be unaffected. Polaris has been shown to co-localize with primary cilia, and these structures have been implicated in the formation of renal cysts. In the orpk pancreas, cilia numbers are reduced and cilia length is decreased. Expression of polycystin-2, a protein involved in PKD, is mislocalized in orpk mice. Furthermore, the cellular localization of beta-catenin, a protein involved in cell adhesion and Wnt signaling, is altered. Thus, polaris and primary cilia function are required for the maturation and maintenance of proper tissue organization in the pancreas.


An atypical catalytic mechanism involving three cysteines of thioredoxin.
Unlike other thioredoxins h characterized so far, a poplar thioredoxin of the h type, PtTrxh4, is reduced by glutathione and glutaredoxin (Grx) but not NADPH:thioredoxin reductase (NTR). PtTrxh4 contains three cysteines: one localized in an N-terminal extension (Cys(4)) and two (Cys(58) and Cys(61)) in the classical thioredoxin active site ((57)WCGPC(61)). The property of a mutant in which Cys(58) was replaced by serine demonstrates that it is responsible for the initial nucleophilic attack during the catalytic cycle. The observation that the C4S mutant is inactive in the presence of Grx but fully active when dithiothreitol is used as a reductant indicates that Cys(4) is required for the regeneration of PtTrxh4 by Grx. Biochemical and x-ray crystallographic studies indicate that two intramolecular disulfide bonds involving Cys(58) can be formed, linking it to either Cys(61) or Cys(4). We propose thus a four-step disulfide cascade mechanism involving the transient glutathionylation of Cys(4) to convert this atypical thioredoxin h back to its active reduced form.


A school outbreak of pandemic (H1N1) 2009 infection: assessment of secondary household transmission and the protective role of oseltamivir.
In mid-June 2009, an outbreak of pandemic (H1N1) 2009 (pH1N1) infection occurred in a secondary school in Hong Kong. We carried out an epidemiological investigation to delineate the characteristics of the outbreak, gauge the extent of secondary household transmission, and assess the protective role of oseltamivir in household contacts. We interviewed pH1N1-confirmed cases using a standardized questionnaire. Sixty-five of 511 students in the school were affected. Of the 205 household contacts identified, 12 were confirmed as cases. All cases recovered. The estimated secondary household attack rate was 5·9% (95% CI 2·7-9·1). Household contacts aged <18 years were about 15 times more likely to be infected than older contacts. Household contacts who had received oseltamivir prophylaxis were less likely to acquire a secondary infection than those who had not (odds ratio=0). The estimated mean household serial interval of pH1N1 virus was 2·8 days (95% CI 2·1-3·4 days).


Connections of midbrain periaqueductal gray in the monkey. II. Descending efferent projections.
1. We have defined the descending efferent projections of the midbrain periaqueductal gray (PAG) by injecting small amounts of [3H]leucine into the various regions of the squirrel monkey PAG. 2. Despite the fact that different regions of the PAG were injected in separate animals, the majority of the brain stem areas labeled remained constant. 3. The PAG exhibited a dense projection to the superior colliculus, the nucleus cuneiformis, and the locus ceruleus. Parts of the reticular formation (nucleus reticularis: pontis oralis, pontis caudalis, gigantocellularis, magnocellularis, and ventralis) received a projection from the PAG, as did the nucleus parabrachial pars lateralis, ambiguous, the nucleus raphe magnus, and raphe pallidus. 4. In contrast to the brain stem, the deep laminae of the nucleus caudalis and the deep laminae of the cervical spinal cord were labeled only after injections of the lateral aspect of the PAG. 5. The main route for the PAG leads to brain stem projections is through the lateral edge of the paramedian reticular formation. The great majority of the anterograde labeling was ipsilateral to the injection although a small contralateral projection was present. 6. These results indicate that the PAG projects to the brain stem and spinal cord in the monkey. Many of the brain stem areas that the PAG projects to are known to project to the spinal cord. These secondary spinal projections coupled with the direct PAG leads to spinal projection provide a wide variety of routes through which the PAG may influence spinal cord activity.


Intra-arterial injection of mesenchymal stem cells to accelerate neointima formation after endovascular stenting in a rabbit model.
Delayed neointima formation over a neurovascular stent is associated with thrombotic complications that can lead to stroke. The purpose of this study was to evaluate whether an intra-arterial injection of mesenchymal stem cells (MSCs) after stent placement leads to improved neointima and reduced thrombus formation over the device. Solitaire stents were placed into the aortas of rabbits that were divided into MSC and control groups. The MSC group received an intra-arterial injection of MSCs through the same microcatheter used for stent deployment. Optical coherence tomography (OCT) was used to evaluate and compare neointima and thrombus formation in a blinded fashion. Explanted specimens were also imaged with scanning electron microscopy (SEM) and evaluated by observers blinded to group allocation using an endothelialization scoring system. The 3-day MSC group was similar to the 7-day controls in terms of stent strut coverage ratio and maximum neointimal thickness, but these values were significantly higher than the 3-day control group based on a hierarchical mixed-effects linear regression analysis. SEM revealed a significantly higher endothelialization score for the MSC group compared with controls at the same time point. There was no difference in thrombus formation between any of the groups. The intra-arterial injection of MSCs after endovascular stenting accelerated early neointima formation but had no effect on thrombus formation in this study. Larger studies are required to verify these findings and determine the durability and mechanism of this effect.


Risk factor of complications requiring neurosurgical intervention in infants with bacterial meningitis.
Among 50 consecutive cases of bacterial meningitis in infants aged 6 months or less, 9 (Group I) were confirmed to have complications requiring neurosurgery during the first 2 weeks of antibiotic treatment. Neurosurgery was performed in 40, 33, and 30% of cases caused by Streptococcus pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, respectively. There were 5 cases of subdural empyema, 1 case of brain abscess, 1 case of subdural empyema and brain abscess, and 2 cases of ventriculitis with severe hydrocephalus. All complications requiring neurosurgery were initially detected by cranial ultrasonography. The other 41 patients who did not undergo neurosurgery were classified as Group II. Comparison of clinical presentations and laboratory findings between the two groups showed that Group 1 contained more patients with a history of inadequate treatment, and longer duration of illness before diagnosis. Except for prolonged disturbance of consciousness, there was no difference between the two groups in clinical and laboratory data on admission or in clinical course during therapy. Due to the high incidence of complications requiring neurosurgical treatment, cost-effective cranial ultrasound is recommended for screening every young infant with bacterial meningitis, especially in cases caused by S. pneumoniae.


The malignant social network: cell-cell adhesion and communication in cancer stem cells.
Tumors contain a vastly complicated cellular network that relies on local communication to execute malignant programs. The molecular cues that are involved in cell-cell adhesion orchestrate large-scale tumor behaviors such as proliferation and invasion. We have recently begun to appreciate that many tumors contain a high degree of cellular heterogeneity and are organized in a cellular hierarchy, with a cancer stem cell (CSC) population identified at the apex in multiple cancer types. CSCs reside in unique microenvironments or niches that are responsible for directing their behavior through cellular interactions between CSCs and stromal cells, generating a malignant social network. Identifying cell-cell adhesion mechanisms in this network has implications for the basic understanding of tumorigenesis and the development of more effective therapies. In this review, we will discuss our current understanding of cell-cell adhesion mechanisms used by CSCs and how these local interactions have global consequences for tumor biology.


Lymphangiosarcoma in a horse.
A 15-year-old Dutch Warmblood mare presented with respiratory distress and anorexia. Clinical examination revealed liquothorax and an abdominal mass. At necropsy, an infiltrating tumour was found in the visceral trunk, continuing through the diaphragm into the mediastinum. Histopathology, immunohistochemistry and electronmicroscopy showed empty channels lined by atypical endothelial cells, and neoplastic cells in a disorganized pattern, consistent with the diagnosis of a lymphangiosarcoma.


Reduction of radiation sensitivity of dry bacterial spores with hydrogen sulfide.
Hydrogen sulfide redtuces the lethal effect of x-rays in dry spores by about 50 percent when given after irradiation, and by approximately 75 percent when present during irradiation. The first effect is the result of removal of radicals that are toxic when combined with oxygen; the second, the removcal of radicals that become toxic in the absence of oxygen. With these results we construct an explanation of the action of sulfhydryl compounds in protection against radiation damage.